Synthesis, SAR, and X-ray structure of novel potent DPPIV inhibitors: oxadiazolyl ketones

Bioorg Med Chem Lett. 2007 Aug 1;17(15):4167-72. doi: 10.1016/j.bmcl.2007.05.046. Epub 2007 May 21.

Abstract

Synthesis of a novel series of DPPIV inhibitors with 1,2,4- and 1,3,4-oxadiazolyl ketone derivatives and its structure-activity relationships are discussed. Compound 18h showed good inhibitory activity against DPPIV and favorable pharmacokinetic properties. In vivo pharmacodynamic efficacy and co-crystal structure of compound 18h with DPPIV is also described.

MeSH terms

  • Animals
  • Crystallography, X-Ray
  • Dipeptidyl Peptidase 4 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors*
  • Dogs
  • Haplorhini
  • Ketones / chemical synthesis*
  • Ketones / chemistry*
  • Ketones / pharmacology
  • Kinetics
  • Models, Molecular
  • Molecular Structure
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology
  • Rats
  • Structure-Activity Relationship

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Ketones
  • Protease Inhibitors
  • Dipeptidyl Peptidase 4